Mafenide is a known anti-microbial agent active against strains of both gram (-) and gram (+) bacteria and some fungi. Its salts are known to have undesirable side effects.
The following described documents provide background information relating to mafenide compounds and phosphanate salts of other compounds.
U.S. Pat. No. 2,288,531 to Klarer relates to 4-aminomethyl-benzenesulphonamide which exhibits antibacterial properties. The Klarer patent specifically relates to the mafenide compound claims which was issued to Winthrop Chemical Company, Inc. in 1942.
U.S. Pat. No. 3,497,599 to Nachod relates to acid addition salts of para-aminomethyl benzene sulfonamide. The acid addition salts exemplified are acetic acid, propionic acid, citric acid, isocitric acid, CIS-aconitic acid, succinic acid, fumaric acid, malic acid and glutamic acid. There are no teachings of a phosphate acid of any kind in Nachod, particularly a phosphanilic acid. The preferred salt disclosed by Nachod is the acetate salt species.
U.S. Pat. No. 4,666,896, issued May 19, 1987 to Warner et al, relates to dinalidixate and diphosphanilate salts of chlorhexidine. Such compositions exhibit synergism as compared with comparable concentrations of chlorhexidine and the respective free acid. There is no teaching that phosphanilate salts of any other drug would indicate any synergism. Further, chlorhexidine is extraordinarily different in structure from mafenide. However, a mixture of phosphanilic acid, trimethoprin, neomycin and streptomycin has also been reported to show synergistic action but not as a salt.
The art has recognized that mafenide has serious drawbacks due to its toxicities of excess osmolality and carbonic anhydrase inhibitory activity. Further, the toxicities of mafenide are increased as the effective amount of mafenide is increased. Presently available mafenide compounds, including salts, all show such toxicities.
Accordingly, there has been a long standing need in the art for compositions having the effect of mafenide which avoid or reduce the excess osmolality and carbonic anhydrase inhibitory activity brought about as compared to mafenide. This need is particularly true in treatments that apply mafenide as an anti-microbial agent in the treatment of burn victims since such high concentrations of mafenide are required for effective anti-microbial activity.